Ustekinumab induced a clinical response and remission in adults with moderate to severe Crohn’s disease who had failed or failed to tolerate other anti–tumor necrosis factor therapies in a phase III induction study of 741 patients (UNITI-1).
The findings were presented at the European Crohn’s and Colitis Organization (ECCO) conference in Amsterdam.
“There is great need for improved therapy for Crohn’s disease, since many patients are failing conventional therapies and also TNF [tumor necrosis factor] antagonists,” lead author Dr. Paul Rutgeerts said in an interview. “Blockade of IL-12/23 is a new mode of action in IBD [inflammatory bowel disease], although this therapy has already been proven effective in the treatment of psoriasis and psoriatic arthropathy,” he said. Data from prior large-scale studies show that ustekinumab is effective in patients with refractory Crohn’s disease, noted Dr. Rutgeerts of University Hospital Gasthuisberg, in Leuven, the Netherlands.
Ustekinumab is approved for treating moderate to severe plaque psoriasis and psoriatic arthritis, and was tested in a phase IIb study for Crohn’s disease in which intravenous ustekinumab induction was followed by surveillance colonoscopy maintenance. This study reviewed the safety and efficacy of intravenous ustekinumab in the same patient population.
The patients were randomized to a 130-mg dose of ustekinumab, weight-based dosing of ustekinumab at 6 mg/kg, or an intravenous placebo. The patients had an average disease duration of 10 years, a baseline median Crohn’s Disease Activity Index (CDAI) score of 317, and a baseline C-reactive protein level of 9.9 mg/L.
After 6 weeks, 34% of patients treated with 6 mg/kg or 130 mg of ustekinumab showed a clinical response, vs. 22% of placebo patients. Clinical response was defined as a reduction from baseline of the CDAI score of at least 100 points. At 8 weeks, patients entered an ongoing maintenance study or were followed up to 20 weeks. Clinical remission (defined as a CDAI score of less than 150 points) at 8 weeks was significantly higher in the 6-mg/kg group (21%) and 130-mg group (16%), compared with the placebo group (7%).
In addition, patients in both ustekinumab groups showed significant improvements in C-reactive protein (CRP), fecal lactoferrin, and calprotectin, and in scores on the Inflammatory Bowel Disease Questionnaire, compared with placebo patients.
The incidence of adverse events, serious adverse events, and infections was not significantly different among the treatment and placebo groups, and no deaths, malignancies, or major adverse events were reported among ustekinumab patients through the 20-week follow-up period.
“The clinical and biologic efficacy of the drug is robust both in patients who have failed conventional drugs and patients who have already failed one, two, or three anti-TNF biologicals,” Dr. Rutgeerts noted. “The approval of Stelara for Crohn’s disease would represent a new treatment option for the more than 5 million people worldwide, including nearly 700,000 Americans, who are living with an inflammatory bowel disease,” he said.
Data from the ongoing IM-UNITI study will demonstrate the long-term efficacy of ustekinumab for Crohn’s patients, but another key step for research would be a head-to-head comparison between ustekinumab and an anti-TNF antibody, Dr. Rutgeerts added.
Dr. Rutgeerts disclosed receiving personal fees from multiple companies including Johnson & Johnson, Amgen, AstraZeneca, Medimmune, Merck, and UCB. The study was supported in part by Janssen.